Quinoline synthesis: Scope and regiochemistry of photocyclisation of substituted benzylidenecyclopentanone O-alkyl and O-acetyloximes

Article abstract of DOI:10.1039/b711620a

Irradiation of substituted 2-benzylidenecyclopentanone O-alkyl and O-acetyloximes in methanol provides a convenient synthesis of alkyl, alkoxy, hydroxy, acetoxy, amino, dimethylamino and benzo substituted annulated quinolines. para-Substituents yield 6-substituted-2,3-dihydro-1H-cyclopenta[b] quinolines with 8-substituted products being obtained from ortho-substituted starting materials. Reactions of meta-substituted precursors are highly regioselective, with alkyl substituents leading to 5-substituted 2,3-dihydro-1H-cyclopenta[b]quinolines and more strongly electron-donating substituents generally resulting in 7-substituted products. 2-Furylmethylene and 2-thienylmethylene analogues yield annulated furo- and thieno-[2,3e]pyridines respectively. Sequential E- to Z-benzylidene group isomerisation and six π-electron cyclisation steps result in formation of a short-lived dihydroquinoline intermediate which spontaneously aromatises by elimination of an alcohol or acetic acid. For 2-benzylidenecyclopentanone O-allyloxime, singlet excited states are involved in both steps. The Royal Society of Chemistry 2007.

Full text of DOI:10.1039/b711620a

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PAPER
www.rsc.org/obc | Organic & Biomolecular Chemistry
Quinoline synthesis: scope and regiochemistry of photocyclisation of
substituted benzylidenecyclopentanone O-alkyl and O-acetyloximes†
Mark Austin, Oliver J. Egan, Raymond Tully and Albert C. Pratt*
Received 30th July 2007, Accepted 24th September 2007
First published as an Advance Article on the web 11th October 2007
DOI: 10.1039/b711620a
Irradiation of substituted 2-benzylidenecyclopentanone O-alkyl and O-acetyloximes in methanol
provides a convenient synthesis of alkyl, alkoxy, hydroxy, acetoxy, amino, dimethylamino and benzo
substituted annulated quinolines. para-Substituents yield 6-substituted-2,3-dihydro-1H-
cyclopenta[b]quinolines with 8-substituted products being obtained from ortho-substituted starting
materials. Reactions of meta-substituted precursors are highly regioselective, with alkyl substituents
leading to 5-substituted 2,3-dihydro-1H-cyclopenta[b]quinolines and more strongly electron-donating
substituents generally resulting in 7-substituted products. 2-Furylmethylene and 2-thienylmethylene
analogues yield annulated furo- and thieno-[2,3e]pyridines respectively. Sequential E- to Z-benzylidene
group isomerisation and six p-electron cyclisation steps result in formation of a short-lived
dihydroquinoline intermediate which spontaneously aromatises by elimination of an alcohol
or acetic acid. For 2-benzylidenecyclopentanone O-allyloxime, singlet excited states are
involved in both steps.
the corresponding quinolines 2a–g, respectively. In contrast, O-
Introduction
methyloximes 1j and 1k underwent only competing geometrical
The quinoline nucleus is widely distributed in nature and is
isomerisation at the carbon–carbon and carbon–nitrogen double
important in the fields of medicinal chemistry and agrochemicals.1
bonds on direct and triplet sensitised excitation resulting, in both
Consequently, though there are numerous syntheses available for
cases, in a photostationary state comprising the four possible
quinoline derivatives,2 versatile routes to new quinoline intermedi-
ates from readily accessible precursors are of interest. Among these
have been a limited number of reports of quinoline formation from
photocyclisation of b-phenyl-a,b-unsaturated oximino systems
(Scheme 1).3 The open-chain oxime 1a,4 O-benzoyloximes 1b–
e5 and O-acetyloximes 1f–i6 underwent 6p-electron cyclisation,
involving both the carbon–nitrogen double bond and the b-aryl
group, followed by elimination of water or benzoic acid, to yield
geometrical isomers, but without accompanying cyclisation.7,8
Prerequisites for photocyclisation are (a) a Z-configuration at
the a,b-double bond, achieved by initial geometrical photoisomeri-
sation, and (b) significant contribution from conformers with an
s-cis orientation at the R1C–CR2 single bond. Systems with this
bond within a ring are forced to adopt an s-cis conformation.
Quinoline formation has been reported where the bond is in-
corporated within a dihydrophenanthrene or acenaphthene ring,9
involving formation of 2l and 2m from 1l and 1m respectively, or
within a cycloalkane, involving formation of 4a–f from 3a–f.10
A broad range of potential quinoline precursors is accessible
by oximation of readily available a-benzylidene ketones. Aryl ring
ortho- or para-substitution should lead to quinolines substituted
at the 5- or 7-ring carbons respectively whereas meta-substitution
School of Chemical Sciences, Dublin City University, Dublin 9, Ireland.
E-mail: albert.pratt@dcu.ie; Fax: +353-(0)1-700-5888; Tel: +353-(0)1-
700-5310
† Electronic supplementary information (ESI) available: Experimental
details and spectral data for the precursors; additional quinoline data.
See DOI: 10.1039/b711620a
Scheme 1 Quinolines from photocyclisation of oximino systems.
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provides the possibility for formation of either 6- or 8-substituted
quinolines.
Unlike 5 and 8, E-2-diphenylmethylenecyclopentanone O-
methyloxime 9 has an appropriately Z-oriented phenyl group
and does not require an additional E/Z-photoisomerisation step
prior to photocyclisation. On irradiation, 9 rapidly formed a
mixture of two products, one of which (Z-9) on further irradiation
transformed to the other, final product 9-phenyl-2,3-dihydro-
1H-cyclopenta[b]quinoline 10. Taking advantage of the suitably
oriented phenyl group in 9, thermal cyclisation was attempted.
However, no reaction occurred on prolonged heating of 9 in
methanol or in ethylene glycol (bp 198 ◦C) under reflux.§
We have used
a range of ortho- and para-substituted
benzylidenecyclopentanone O-alkyloximes and O-acetyloximes
(Scheme 3) to examine the scope of the photocyclisation–
elimination reaction as a route to annulated quinolines of
the 2,3-dihydro-1H-cyclopenta[b]quinoline family, and the cor-
responding meta-substituted compounds (Scheme 6) to examine
regiochemical outcomes. The required compounds were obtained
by standard oximation procedures from the appropriate 2-
benzylidenecyclopentanones which were in turn readily available
from reaction of N-(1-cyclopentenyl)morpholine with the corre-
sponding aromatic aldehydes.
ortho- and para-Substituted benzylidene systems
The ortho- and para-methyl-, and ortho- and para-methoxy-ben-
zylidene O-methyloximes 11a–d cyclised to the corresponding
8- and 6-substituted¶ 2,3-dihydro-1H-cyclopenta[b]quinolines
12a–d on irradiation in methanol (Scheme 3). Similarly the
para-hydroxy-, para-acetoxy-, and para-N,N-dimethylamino-
benzylidene O-acetyloximes 11e–g and the para-amino-
benzylidene oxime 11h cyclised to the quinolines 12e–h respec-
tively. In each case, TLC analysis showed the initial formation of
a number of products, presumed to be the various geometrical
Results
Unsubstituted benzylidenecyclopentanone O-alkyloximes
Irradiation of E,E-O-allyloxime 5‡ in methanol resulted in
initial E,Z-isomerisation at the carbon–nitrogen and carbon–
carbon double bonds (Scheme 2). However, isomerisation was
accompanied by the slower formation of quinoline 7 as the final
product, involving photocyclisation of the E,Z-isomer (and/or
the Z,Z-isomer) to dihydroquinoline 6, followed by rapid elimi-
nation of allyl alcohol. Quinoline 7 was also obtained from the
corresponding O-methyloxime 8.
Scheme 3 Cyclisations involving ortho- and para-substituents.
§ The analogous open-chain O-acetyloxime of 4,4-diphenylbut-3-en-
=
=
2-one (Ph2C CHCMe NOAc) undergoes conversion to 2-methyl-4-
phenylquinoline at 187 ◦C. Semi-empirical calculations have been used
in support of a pericyclic mechanism involving disrotatory closure to
an intermediate analogous to 6, followed by subsequent intramolecular
elimination of acetic acid via a cyclic transition state.11 O-Methyloxime 1l
undergoes closure–elimination above 120◦C to yield 2l.9 The low activation
barrier was ascribed to aromatic stabilisation of the cyclised intermediate
due to generation of a phenanthrene unit prior to methanol elimination.
In the case of 9, however, no such stabilisation is possible.
¶ Nomenclature convention results in different numbering of the aromatic
ring positions for quinolines and 2,3-dihydro-1H-cyclopenta[b]quinolines.
Benzenoid ring positions 5, 6, 7 and 8 in the former correspond to positions
8, 7, 6 and 5 respectively in the latter.
Scheme 2 Cyclisations without aryl substituents.
‡ Compound 5 was obtained as a single isomer on reaction of 2-
benzylidenecyclopentanone with O-allylhydroxylamine. In ethyl acetate 5
underwent only E,Z-photoisomerisation to a photostationary state com-
prising the E,E- (19%), Z,E- (48%), E,Z- (23%) and Z,Z- (10%) isomers.
These were separated chromatographically and their stereochemistries
assigned.
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isomers and, on further irradiation, these underwent conver-
sion to the corresponding 2,3-dihydro-1H-cyclopenta[b]quinoline.
2-Benzylidenecyclohexanone O-methyloxime similarly yielded
tetrahydroacridine 4e.
In marked contrast ortho- and para-nitro-, ortho- and para-
chloro- and para-cyano-benzylidenecyclopentanone O-methyl-
oximes 11i–m, and 2,4-difluorobenzylidene O-acetyloxime 11n
were converted to complex mixtures whose separation was not
pursued further.
Other participating p-systems
Other p-systems may replace the 2p-electron contribution of
the b-phenyl group in these systems (Scheme 4). Thus 2-(1-
naphthylmethylene)cyclopentanone O-methyloxime yielded fused
benzo[f ]quinoline 13 and 2-(1-phenothiazinylmethylene)cyclo-
pentanone O-acetyloxime was converted to the novel pyrido-
[3,2-a]phenothiazine 14. 2-(2-Furylmethylene)cyclopentanone
O-methyloxime yielded N,O-heterocycle 15 and N,S-heterocycle
16 was similarly obtained from 2-(2-thienylmethylene)cyclo-
pentanone O-acetyloxime. Compound 17, a photoisomer of
2-cinnamylidenecyclopentanone O-acetyloxime, also cyclised,
yielding pyridine 18 and requiring the adoption of an s-cis
arrangement for the open-chain dienyl unit in addition to prior
E,Z-isomerisation at the 2-exo methylene unit to achieve a viable
cyclic transition state for carbon–nitrogen bond formation.
Scheme 5 Alternatives with meta-substituents.
Scheme 4 Other cyclisations.
meta-Substituted benzylidene systems
Scheme 6 Cyclisations with meta-substituents.
Cyclisation is possible for meta-substituted benzylidene derivatives
either from rotamer 19, giving 5-substituted-2,3-dihydro-1H-
cyclopenta[b]quinoline 21, or from rotamer 22, giving the 7-
substituted isomer 24 (Scheme 5)ꢀ.
3,4-dimethyl- and 3-methyl-4-methoxy substrates 25b and 25c
giving 5,6-dimethyl- and 5-methyl-6-methoxy-2,3-dihydro-1H-
cyclopenta[b]quinolines 26b and 26c respectively. Increasing the
steric demand of the meta-alkyl substituent again resulted in strong
preference for cyclisation–elimination involving the crowded aryl
A meta-methyl substituent results in closure at the aryl
2-position, ortho to the methyl group (Scheme 6). 2-(3-
Methylbenzylidene)cyclopentanone O-methyloxime 25a yielded
a single photoproduct, 5-methyl compound 26a. Inclusion of
an additional ring substituent, a para-methyl or para-methoxy
group, similarly resulted in closure at the 2-position, with
2-position, with meta-t-butyl compound 25d giving 5-t-butyl-2,3-
∗∗
dihydro-1H-cyclopenta[b]quinoline 26d
.
In contrast, a meta-methoxy group results in closure at
the aryl 6-position, para to the methoxy substituent. Both 3-
methoxybenzylidene O-methyloxime 25e and O-acetyloxime 25f
ꢀPossible in principle for ortho-substituted benzylidene analogues, cycli-
sation with elimination of a 2-substituent (R) has not been observed,
presumably because of the difficulty of eliminating a species such as
MeOR or AcOR. Replacement of 2-substituents has been observed for
2-substituted stilbene oxidative cyclisations, involving elimination of HR.12
∗∗
Prior to recrystallisation, the 1H-NMR spectrum of the chro-
matographed product showed it to be 5-t-butyl-2,3-dihydro-1H-
cyclopenta[b]quinoline (92%) together with a small amount of another
t-butyl-containing component (8%), possibly the other regioisomer.
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yielded a single photoproduct, 7-methoxy compound 27e. In-
corporation of an additional substituent, methyl or methoxy, in
the para-position again resulted in closure at the aryl 6-position,
with 3,4-dimethoxy and 3-methoxy-4-methyl compounds 25g
and 25h giving 6,7-dimethoxy- and 6-methyl-7-methoxy-2,3-
dihydro-1H-cyclopenta[b]quinolines 27g and 27h respectively. 2,5-
Dimethoxybenzylidene O-acetyloxime 28 (Scheme 7), with the
position para to the meta-methoxy group blocked by the 2-
methoxy substituent, cyclised at the vacant ortho site to give 5,8-
dimethoxy-2,3-dihydro-1H-cyclopenta[b]quinoline 29.
The four geometrical isomers of O-allyloxime 5 exhibit strong
uv absorption in the 300 nm region, probably due to the p,p*
band of the conjugated a,b-unsaturated system submerging the
much weaker n,p* band. With n,p* transitions in such systems
being generally localised at the carbon–nitrogen double bond it
is likely that cyclisation of 5 requires a lowest energy p,p* excited
state. In ethyl acetate, cyclisation of 5 does not occur,‡ suggesting
a lowest energy n,p* transition in this solvent. Methanol may
assist the formation of quinoline 7 from 5 by hydrogen bonding
to the nitrogen lone pair of the O-allyloxime thereby ensuring a
lowest energy p,p* excited state and methanol may also facilitate
elimination of allyl alcohol from dihydroaromatic intermediate 6.
In acetonitrile formation of 7 from 5 is approximately 25 times
less rapid, consistent with hydrogen-bonding playing a role in
facilitating the photocyclisation–elimination process. The rate
of quinoline formation was approximately doubled for both
meta- and para-N,N-dimethylaminobenzylidene O-acetyloximes,
25j and 11g respectively, by inclusion of a small amount of triflu-
oroacetic acid but, whereas the yield of quinoline 27j from meta-
dimethylaminobenzylidene oxime acetate 25j improved (from 6%
to 35%) in the presence of the acid, no improvement in cyclisation
yield (26%) was observed for para-dimethylaminobenzylidene
oxime acetate 11g. Methanol with added mineral acid has been
used as the medium for quinoline formation from oximes 3a–d,f.10
Scheme 7
Other electron-donating substituents having a nitrogen or
oxygen in the meta-position of the benzylidene group similarly
resulted in closure at the aryl-6 position (Scheme 6). Thus 3-
hydroxy- and 3-N,N-dimethylaminobenzylidene O-acetyloximes
25i and 25j, also the 3-aminobenzylidene oxime 25k, photocyclised
to the corresponding 7-substituted products 27i–k, respectively.
In contrast to these cyclisations from which a single product
was isolated, irradiation of 3-acetoxybenzylidene O-acetyloxime
25l resulted in competitive closure, involving both the aryl-6
and aryl-2 positions, and giving both 7-acetoxy and 5-hydroxy
products 27l and 26lꢁ. The deacetylation step leading to 26lꢁ must
have occurred subsequent to cyclisation since, if loss of acetyl
from 25l had preceded cyclisation, the resulting initially-formed
3-hydroxybenzylidene O-acetyloxime 25i would have cyclised to
7-hydroxy compound 27i rather than to 5-hydroxy compound
26lꢁ. No accompanying photo-Fries rearrangement products were
isolated from this reaction.
As observed for the analogous ortho- and para-substituted ben-
zylidenecyclopentanone derivatives 11j–n, irradiation of 3-nitro-,
3-chloro-, 3-cyano- and 3-fluoro-benzylidene O-acetyloximes
25m–p proved not to be synthetically useful. Only complex product
mixtures were obtained and these were not investigated further.
2-(2-Naphthylmethylene)cyclopentanone O-acetyloxime 30a
and O-methyloxime 30b (Scheme 7) cyclised at the naphthyl 1-
position to give 9,10-dihydro-8H-benzo[h]cyclopenta[b]quinoline
31, rather than at the naphthyl 3-position.13
Analogy with stilbene cyclisation
The photocyclisation–elimination process for quinoline synthesis
is analogous to the well-established conrotatory photocyclisa-
tion process for 1,3,5-hexatrienes, the most studied being the
oxidative photoconversion of stilbenes to phenanthrenes14–16 via
dihydrophenanthrene intermediates which aromatise either in
the presence of oxygen or, more commonly, in the presence of
an added oxidant such as iodine. Though chloro, fluoro and
cyano substituents are compatible with stilbene photoconversion
to phenanthrenes,14c,15,17 also with quinoline formation from p-
chlorophenyl O-benzoyloxime 1e,5 this is not the case for quino-
line formation from benzylidenecyclopentanone oxime ethers or
acetates 11k–n and 25n–p. Possibilities for this difference in
behaviour include (a) enhanced intersystem crossing for these par-
ticular b-aryl-a,b-unsaturated oxime derivatives, with alternative
reaction pathways being available to the triplet excited state,††
(b) the nature of their lowest excited singlet states, with n,p*
states being generally less amenable to 6p-electron cyclisation and
(c) the intervention of other reaction pathways, possibly involving
radicals and leading to alternative reaction outcomes. The lack of
photocyclisation when electron-withdrawing groups are present
on the b-aryl ring may imply the necessity for a polarised transition
state in which electron density is transferred through the p-system
from the aryl ring to the oximino nitrogen, facilitating aryl–
nitrogen bond formation and detachment of the leaving group.
Discussion
Regioselectivity
Excited state considerations
In general2-naphthylhomologues of stilbene (Scheme 8)havebeen
found15 to undergo oxidative photocyclisation at the 1-naphthyl
The inclusion of various concentrations (up to 1.0 M) of the
triplet quencher isoprene in methanol solutions of E,E-5 did not
affect the course of product evolution, consistent with both the
isomerisation and cyclisation processes arising from singlet excited
states on direct irradiation.
††For the currently included substituents this seems likely only for the
nitro group. There do not appear to have been any reports of oxidative
photocyclisations of nitrostilbenes.
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Scheme 8 Alternative cyclisation options from ground state rotamers.
Scheme 9
position, though more recent studies have shown that reaction
may also occur at the naphthyl 3-position.
been reported.25 The 2-vinyl analogues are similarly converted
to the corresponding isoquinolines. These outcomes may also
be rationalised by a six p-electron cyclisation process. How-
ever, iminyl radicals 36 have been proposed as intermediates
in the formation of 35, generated by nitrogen–oxygen bond
photocleavage. Such homolysis, yielding acyloxy and aryliminyl
radicals, occurs in the photochemistry of O-acyloxime derivatives
of simple aromatic carbonyl compounds such as benzaldehyde,
acetophenone, benzophenone and 9-fluorenone and has been used
as a convenient source of carbon-centred radicals for synthetic
investigations26,27 and as a photochemical source of amines for
polymer cross-linking, the amines resulting from hydrolysis of the
imines formed following nitrogen–oxygen bond cleavage.28
Whether the phenanthridines 35 are formed by a six p-electron
photocyclisation process in competition with radical formation,
or are formed through the intermediacy of photogenerated
iminyl radicals 36, is unclear. Iminyl radicals may be readily
generated by a variety of non-photochemical routes,29 and there
is precedence for radicals analogous to 36 undergoing closure
to phenanthridines and quinolines30 though five-membered ring
formation has been reported to accompany quinoline formation
in favourable cases.31
Benzaldehyde O-alkyloximes undergo very inefficient carbon–
nitrogen bond photocleavage on direct or triplet sensitised
excitation,32 though the efficiency of radical formation from
benzaldehyde O-acyloximes can be increased by the use of triplet
photosensitisers.33 However, given that the compounds that com-
prise the present study lack the phenone O-acyl or O-alkyloxime
functionality, which seems to be essential for such cleavage on
direct excitation, it can be concluded that these cyclisations
proceed by the proposed six p-electron photocyclisation§§. This
conclusion is supported by the absence of reports of nitrogen–
oxygen bond homolysis on direct or triplet sensitised excitation
of a wide range of other O-alkyl and O-acyloximes such as ace-
tophenone O-methyloxime,35 acetonaphthone O-methyloxime,36
b-phenyl-a,b-unsaturated oximino systems 1a–m,4–10 b-ionone O-
ethyloxime,37 b,c-unsaturated oxime acetates38 and cholestanone
O-acetyloximes.39
Thus the ground state rotamers 32 and 33 of Z-di(2-
naphthyl)ethene undergo competitive 1,1ꢁ- and 1,3ꢁ-cyclisation
respectively to give the corresponding dihydrophenanthrenes on
excitation,19,20‡‡ and oxidative conditions can be adjusted to yield
predominantly dibenzo[c,g]phenanthrene or dibenzo[b,g]phenan-
threne respectively.19,21 Prediction of the preferred cyclisation route
for diarylethenes has been assisted by the use of calculated free
valence numbers or electronic overlap populations22 as measures
of reactivity for electrocyclic processes, with most success being
for polycyclic aromatic substituents.
Though more favourable substituent-dependent frontier orbital
overlap in the transition state for cyclisation of one of the rotamers
of a meta-substituted stilbene may play a contributing part in
determining regioselectivity, it would not seem to be a determining
one since, for many meta-substituted stilbenes, approximately
equal amounts of the corresponding 2- and 4-substituted phenan-
threnes are found.14c,23 Recent consideration of the photocy-
clisations of styrylpyridines and 2-aminostyrylpyridines24 has
pointed to the role of rotamers and led to the suggestion
that the regiochemical outcome for a meta-substituted stilbene
analogue is determined by the relative rates of oxidation and
ring-opening of the intermediate dihydrophenanthrenes. Similar
substituent-related competition between ring-opening and elim-
ination steps for the non-aromatic intermediates from meta-
substituted benzylidenecyclopentanone oxime derivatives, 20 and
23 from rotamers 19 and 22 respectively (Scheme 5), probably also
determines whether 5-substituted or 7-substituted products, 21 or
24 respectively, are obtained. The nature and interactions of these
substituent effects has yet to be determined.
Other observations
The nature of the group eliminated does not affect the cyclisation
outcome. O-Allyloxime 5, O-methyloxime8 and the corresponding
O-acetyloxime yielded 2,3-dihydro-1H-cyclopenta[b]quinoline 7.
Similarly O-acetyloxime 30a and O-methyloxime 30b yielded 9,10-
dihydro-8H-benzo[f ]cyclo-penta[b]quinoline 31 and 7-methoxy-
2,3-dihydro-1H-cyclopenta[b]quinoline 27e was obtained from
both O-methyloxime 25e and O-acetyloxime 25f. Initial studies
were undertaken with O-methyloximes but, when it became ap-
parent that the cyclisation outcome was independent of the nature
of the leaving group, the more readily prepared O-acetyloximes
were subsequently used.
Conclusions
This photocyclisation–elimination process provides a conve-
nient route to a wide variety of substituted 2,3-dihydro-1H-
cyclopenta[b]quinolines from readily accessible precursors and has
Photocyclisation of the O-acetyloximes 34 of 2-phenyl-
benzaldehyde, 2-phenylacetophenone and 2-phenylbenzophenone
to the corresponding phenanthridines 35 (Scheme 9) has recently
§§In the presence of excited 1,5-dimethoxynaphthalene (DMN) as a single
electron transfer agent, c,d-unsaturated ketone O-acyl and O-methyloximes
are converted to radical anions, which cyclise by an iminyl radical mecha-
nism to 3,4-dihydro-2H-pyrroles. Alternatively, triplet energy transfer from
excited DMN may result in iminyl radical formation and cyclisation.34 Such
reaction conditions were absent from the present study.
‡‡The principle of non-equilibration of excited rotamers (NEER) implies
that the ground state populations of 32 and 33 determine the excited state
populations.18
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the potential for extension to the synthesis of numerous novel
fused pyridines/quinolines of biomolecular interest derived, for
example, from terpenoid or steroidal ketones.
petroleum–ethyl acetate as eluent, prior to recrystallisation. Unless
otherwise stated, recrystallisation was from light petroleum–ethyl
acetate.
2,3-Dihydro-1H-c◦yclopenta[b]quinoline 7. (24% from 5; 29%
◦
from 8), mp 60–61 C (lit.,41 60–61 C); dH 2.18 (2H, qn, J 7.4,
Experimental section
CH2CH2CH2), 3.06 (2H, t, J 7.4, CH2Ar), 3.14 (2H, t, J 7.4,
CH2Ar), 7.43 (1H, t, J 7.7) and 7.59 (1H, t, J 7.9) (arH-7 and
arH-6), 7.70 (1H, d, J 7.7, arH-8), 7.85 (1H, br s, arH-9) and 8.00
(1H, d, J 7.9, arH-5); dC 23.62, 30.50, 34.60 (3 × CH2), 125.49,
127.43, 128.30 and 128.51 (benzenoid-CH), 130.29 (pyridyl-CH),
127.37, 135.77, 147.48 and 167.91 (quaternary Cs).
NMR spectra were recorded on a Bruker AC-400 instrument
operating at 400 MHz for 1H and 100 MHz for 13C. Unless
otherwise stated, spectra were recorded using CDCl3 as solvent,
with Me4Si as internal standard. TLC was on silica gel plates
containing a fluorescent indicator (Riedel-de-Haen, DC-Cards
SiF, layer thickness 0.2 mm). Light petroleum for recrystallisation
had bp 80–100 ◦C, unless stated otherwise. Yields were not
optimised. Melting points are uncorrected. Satisfactory elemental
analyses were obtained for all new compounds.
Photochemical reactions were carried out using a water-cooled
immersion well containing a Photochemical Reactors 400 W
medium pressure mercury vapour lamp fitted with a Pyrex filter
(k > 300 nm). Solutions for photochemistry used high purity grade
solvents which were deoxygenated by passing a stream of nitrogen
or argon through the solution for 30 minutes prior to irradiation
and the inert gas atmosphere was maintained over the solutions
during irradiation.
9-Phenyl-2◦,3-dihydro-1H-cyclopenta[b]qui◦noline
10. (72%),
mp 132–134 C (methanol) (lit.,42 134–135 C); dH 2.16 (2H, qn,
J 7.5, CH2CH2CH2), 2.90 (2H, t, J 7.5, CH2Ar), 3.24 (2H, t, J
7.5, CH2Ar), 7.36 (3H, m), 7.49 (3H, m) and 7.62 (2H, m) (8 ×
arH), 8.08 (1H, d, J 8.4, arH-5); dC 23.42, 30.22, 35.08 (3 × CH2),
125.39, 125.54, 126.09, 127.88, 128.13, 128.39, 128.68, 129.18,
133.55, 136.62, 142.59, 147.81 and 167.31 (13 × arC).
8-Methyl-2,3-dihydro-1H-cyclopenta[b]quinoline 12a. (35%),
mp 64–65 ◦C (light petroleum); dH 2.21 (2H, qn, J 7.4,
CH2CH2CH2), 2.65 (3H, s, Me), 3.11 (2H, t, J 7.4, CH2Ar), 3.16
(2H, t, J 7.4, CH2Ar), 7.28 (1H, d, J 8.4, arH-7), 7.50 (1H, t, J 8.4,
arH-6), 7.87 (1H, d, J 8.4, arH-5) and 8.07 (1H, s, arH-9); dC 18.83
(Me), 23.65, 30.72 and 34.50 (3 × CH2), 126.12, 126.53, 126.75,
126.89, 127.94, 133.98, 135.22, 147.68 and 167.23 (9 × arC).
Preparative details and nmr spectra are reported here for the
annulated quinolines. Other analytical data for the quinolines, also
experimental and spectral data for the other compounds included
in this work, are reported in the ESI accompanying this paper.†
6-Methyl-2,3-dihydro-1H-cyclopenta[b]quinoline 12b. (37%),
mp 86–88 ◦C (light petroleum); dH 2.20 (2H, qn, J 7.5,
CH2CH2CH2), 2.54 (3H, s, Me), 3.07 (2H, t, J 7.5, CH2Ar), 3.15
(2H, t, J 7.5, CH2Ar), 7.30 (1H, d, J 8.2, arH-7), 7.63 (1H, d, J
8.2, arH-8), 7.79 (1H, s, arH-5) and 7.85 (1H, s, arH-9); dC 21.82
(Me), 23.66, 30.48 and 34.63 (3 × CH2), 125.37, 127.07, 127.70,
128.98, 130.15, 131.93, 134.73, 138.49 and 167.80 (9 × arC).
Preparation of 2-benzylidenecyclopentanones
Preparations involved reaction of the morpholine enamine of
cyclopentanone with the appropriate aromatic aldehyde.40
Preparation of 2-benzylidenecyclopentanone oximes
Preparations involved reaction of the ketones with hydroxylamine
hydrochloride in pyridine.
8-Methoxy-2,3-dihydro-1H-cyclopenta[b]quinoline 12c. (48%),
mp 76–77 ◦C (light petroleum); dH 2.21 (2H, qn, J 7.6,
CH2CH2CH2), 3.09 (2H, t, J 7.6, CH2Ar), 3.15 (2H, t, J 7.6,
CH2Ar), 3.99 (3H, s, MeO), 6.81 (1H, d, J 8.1, arH-7), 7.51 (1H,
t, J 8.1, arH-6), 7.61 (1H, d, J 8.1, arH-5) and 8.33 (1H, s, arH-9);
dC 23.61, 30.64, 34.62 (3 × CH2), 55.68 (OMe), 103.62, 119.56,
120.89, 125.06, 128.17, 134.76, 148.34, 155.07 and 168.05 (9 ×
arC).
Preparation of benzylidenecyclopentanone O-methyloximes
Preparations involved reaction of the required oxime with excess
dimethyl sulfate in the presence of sodium hydroxide.
Preparation of benzylidenecyclopentanone O-acetyloximes
Preparations involved reaction of the required oxime with acetyl
chloride in pyridine.
6-Methoxy-2,3-dihydro-1H-cyclopenta[b]quinoline 12d. (53%),
mp 58–60 ◦C (light petroleum); dH 2.20 (2H, qn, J 7.5,
CH2CH2CH2), 3.06 (2H, t, J 7.5, CH2Ar), 3.15 (2H, t, J 7.5,
CH2Ar), 3.93 (3H, s, OMe), 7.12 (1H, dd, J 8.8, 2.2, arH-7), 7.37
(1H, d, J 2.2, arH-5), 7.62 (1H, d, J 8.8, arH-8) and 7.82 (1H, s,
arH-9); dC 23.58, 30.32, 34.59 (3 × CH2), 55.35 (OMe), 106.95,
118.20, 122.34, 128.30, 130.23, 133.31, 148.98, 159.86 and 167.98
(9 × arC).
General procedure for synthesis of
2,3-dihydro-1H-cyclopenta[b]quinolines
A methanol solution (250–350 cm3) of the appropriate O-
methyloxime, O-acetyloxime or oxime (2.5–10.0 × 10−3 M) was
irradiated under the standard conditions. Reaction progress was
monitored by TLC using light petroleum–ethyl acetate [ethanol in
the cases of 12g, 14 and 27j]. In general, a number of products ap-
peared soon after irradiation began and on continued irradiation,
one of these became the sole/predominant product, at which time
irradiation was discontinued. Removal of the methanol yielded the
crude 2,3-dihydro-1H-cyclopenta[b]quinoline. Purification was
by recrystallisation or by chromatography on silica, with light
6-Hydroxy-2,3-dihydro-1H-cyclopenta[b]quinoline 12e. (36%),
mp 168–169 ◦C; dH (CD3)2SO 2.09 (2H, qn, J 7.5, CH2CH2CH2),
2.93–3.01 (4H, m, CH2Ar), 7.00 (1H, dd, J 8.8, 2.2, arH-7), 7.24
(1H, d, J 2.2, arH-5), 7.50 (1H, d, J 8.8, arH-8), 7.73 (1H, s,
arH-9) and 9.65 (1H, br s, OH); dC (CD3)2SO 22.64, 29.27, 33.59
(3 × CH2), 109.30, 117.16, 120.73, 127.36, 129.43, 131.50, 148.06,
157.06 and 166.67 (9 × arC).
This journal is
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6-Acetoxy-2,3-dihydro-1H-cyclopenta[b]quinoline 12f. (36%),
mp 96–97 ◦C; dH 2.21 (2H, qn, J 7.6, CH2CH2CH2), 2.36 (3H, s,
MeCO), 3.08 (2H, td, Jt 7.6, Jd 1.0, CH2Ar), 3.08 (2H, t, J 7.6,
CH2Ar), 7.24 (1H, dd, J 8.8, 2.4, arH-7), 7.71–7.74 (2H, m, arH-
5/8) and 7.88 (1H, br s, arH-9); dC 21.19 (Me), 23.58, 30.42, 34.57
(3 × CH2), 119.64, 120.80, 125.40, 128.34, 130.15, 135.62, 147.91,
dC 23.83, 30.45, 33.87 (3 × CH2), 124.43, 125.70, 128.66, 131.24,
133.10, 154.64 and 164.39 (7 × arC).
2-Phenyl-6,7-dihydro-5H-cyclopenta[b]pyridine 18. (10%), mp
79–80 ◦C (lit.,43 81–82 ◦C); dH 2.04 (2H, qn, J 7.6, CH2CH2CH2),
2.84 (2H, t, J 7.6, CH2Ar), 2.96 (2H, t, J 7.6, CH2Ar), 7.24 (1H, tt,
J 7.6, 1.2), 7.32 (3H, m), 7.42 (1H, d, J 7.6) and 7.81 (2H, m) (7 ×
arH); dC 23.23, 30.48, 34.41 (3 × CH2), 118.25, 126.89, 128.32,
128.64, 132.56, 135.41, 140.00, 155.87 and 165.83 (9 × arC).
5-Methyl-2,3-dihydro-[1H]-cyclopenta[b]quinoline 26a. (32%),
mp 92–94 ◦C (light petroleum); dH 2.19 (2H, qn, J 7.4,
CH2CH2CH2), 2.80 (3H, s, Me), 3.05 (2H, t, J 7.4, CH2), 3.16
(2H, t, J 7.4, CH2), 7.32 (1H, t, J 8.3, arH-7), 7.44 (1H, d, J 8.3,
arH-8 or -6), 7.55 (1H, d, J 8.3, arH-6 or -8) and 7.81 (1H, s, arH-
9); dC 18.32 (Me), 23.72, 30.43, 34.87 (3 × CH2), 125.04, 125.52,
127.22, 128.54, 130.46, 135.08, 136.20, 146.63 and 166.88 (arC).
=
150.46, 168.57 and 169.41(9 × arC + C O).
6-N,N-Dimethylamino-2,3-dihydro-1H-cyclopenta[b]quinoline
12g. (26%), mp 104–106 ◦C; dH 2.16 (2H, qn,
J 7.5,
CH2CH2CH2), 3.01 (2H, td, Jt 7.5, Jd 1.0, CH2Ar), 3.06 (6H, s,
NMe2), 3.09 (2H, t, J 7.5, CH2Ar), 7.13 (1H, dd, J 8.8, 2.6, arH-
7), 7.14 (1H, d, J 2.6, arH-5), 7.55 (1H, d, J 8.8, arH-8) and 7.72
(1H, s, arH-9); dC 23.60, 30.33, 34.70 (3 × CH2), 40.60 (NMe2),
107.11, 115.15, 119.93, 127.86, 130.08, 131.41, 149.20, 150.67 and
167.77 (9 × arC).
A similar yield (24%) of 6-N,N-dimethylamino-2,3-dihydro-
1H-cyclopenta[b]quinoline 12g was obtained following similar
irradiation in the presence of added trifluoroacetic acid (1 equiv.,
3.6 mM). Isolation, by diethyl ether extraction and chromatogra-
phy, followed initial adjustment of the irradiated solution to pH
∼8 by addition of 10% aq. sodium carbonate solution.
5,6-Dimethyl-2,3-dihydro-1H-cyclopenta[b]quinoline
26b.
(17%), mp 90–91 ◦C; dH 2.10 (2H, qn, J 7.5, CH2CH2CH2), 2.40
(3H, s, Me), 2.67 (3H, s, Me), 2.98 (2H, t, J 7.5, CH2), 3.09 (2H,
t, J 7.5, CH2), 7.19 (1H, d, J 8.2) and 7.40 (1H, d, J 8.2) (arH-7
and arH-8), 7.71 (1H, s, arH-9); dC 13.48, 20.64 (2 × Me), 23.75,
30.33, 34.88 (3 × CH2), 124.45, 125.55, 128.17, 130.46, 133.49,
133.97, 135.91, 146.53 and 166.75 (9 × arC).
6-Amino-2,3-dihydro-1H-cyclopenta[b]quinoline 12h. (36%),
mp 94–96 ◦C; dH 2.15 (2H, qn, J 7.6, CH2CH2CH2), 3.02 (2H,
td, Jt 7.6, Jd 1.0, CH2Ar), 3.26 (2H, t, J 7.6, CH2Ar), 4.22 (2H,
br, NH2), 6.89 (1H, dd, J 8.5, 2.3, arH-7), 7.36 (1H, s, arH-9),
7.50 (1H, d, J 8.5, arH-8) and 7.80 (1H, d, J 2.3, arH-5); dC 22.73,
30.31, 31.17 (3 × CH2), 99.83, 118.84, 121.96, 123.55, 129.47,
133.34, 141.82, 148.14 and 152.25 (9 × arC).
5-Methyl-6-methoxy-2,3-dihydro-1H -cyclopenta[b]quinoline
26c. (15%), mp 89–91 ◦C; dH 2.12 (2H, qn, J 7.5, CH2CH2CH2),
2.62 (3H, s, Me), 2.98 (2H, t, J 7.5, CH2), 3.10 (2H, t, J 7.5, CH2),
3.90 (3H, s, OMe), 7.15 (1H, d, J 9.0, arH-7), 7.50 (1H, d, J 9.0,
arH-8) and 7.73 (1H, s, arH-9); dC 9.94 (Me), 23.78, 30.30, 35.00
(3 × CH2), 56.41 (OMe), 112.25, 121.54, 122.47, 125.56, 130.47,
132.81, 147.15, 156.68 and 167.65 (9 × arC).
9,10-Dihydro-8H-benzo[f ]cyclopenta[b]quinoline 13. (69%),
mp 126–128 ◦C (light petroleum); dH 2.27 (2H, qn, J 7.4,
CH2CH2CH2), 3.19 (2H, t, J 7.4, ArCH2), 3.22 (2H, J 7.4,
ArCH2), 7.61 (1H, t, J 7.4) and 7.66 (1H, t, J 7.4) (arH-2/3), 7.92
(3H, m; arH-1/4/5), 8.60 (1H, d, J 7.8, arH-6) and 8.74 (1H, s,
arH-11); dC 23.66, 30.92, 34.47 (3 × CH2), 122.36, 123.99, 125.75,
126.60, 126.69, 127.91, 128.61, 129.63, 129.82, 131.48, 135.82,
147.08 and 166.86 (13 × arC).
∗∗
5-t-Butyl-2,3-dihydro-1H-cyclopenta[b]quinoline 26d. (13%),
mp 62–64 ◦C (light petroleum); dH 1.70 (9H, s, CMe3), 2.20 (2H,
qn, J 7.6, CH2CH2CH2), 3.07 (2H, t, J 7.6, ArCH2), 3.14 (2H, t,
J 7.6, ArꢁCH2), 7.36 (1H, t, J 7.6, arH-7), 7.58 (2H, coincident
doublets, J 7.6, arH-6 and arH-8) and 7.83 (1H, s, arH-9); dC
22.61, 28.68, 29.39, 30.03, 33.82 (3 × CH2, CMe3 and CMe3),
123.73, 123.78, 125.35, 127.04, 129.50, 132.94, 145.59, 146.31 and
163.70 (9 × arC).
1,2,3,12-Tetrahydrocyclopenta[5,6]pyrido[3,2-a]phenothiazine 14.
(12%), mp 67–68 ◦C; dH 2.14 (2H, qn, J 7.2, CH2CH2CH2), 2.44
(2H, t, J 7.2) and 3.29 (2H, t, J 7.2) (2 × CH2Ar), 6.38 (1H, s,
NH), 6.68 (1H, dd, J 7.2, 0.8), 6.95 (2H, m), 7.10 (3H, m) and 7.32
(1H, dd, J 8.8, 1.0) (7 × arH); dC 16.69, 24.56, 29.78 (3 × CH2),
107.64, 116.34, 116.46, 116.74, 117.19, 119.18, 123.02, 123.77,
124.74, 126.52, 127.56, 128.25, 136.08, 136.18 and 137.56 (15 ×
arC).
7-Methoxy-2,3-dihydro-1H-cyclopenta[b]quinoline 27e. (63%
◦
from both 25e and 25f), mp 96–97 C (light petroleum) (lit.44
99–100 ◦C); dH 2.72 (2H, qn, J 7.9, CH2CH2CH2), 3.58 (2H, t,
J 7.9, ArCH2), 3.65 (2H, t, J 7.9, ArCH2), 4.42 (3H, s, OMe),
7.53 (1H, d, J 2.5, arH-8), 7.81 (1H, dd, J 8.9, 2.5, arH-6), 8.32
(1H, s, arH-9) and 8.45 (1H, d, J 8.9, arH-5); dC 23.28, 30.18, 33.93
(3 × CH2), 55.06 (OMe), 105.16, 120.07, 127.87, 128.93, 129.46,
135.52, 143.05, 156.70 and 164.98 (9 × arC).
6,7-Dihydro-5H-cyclopenta[b]furo[2,3-e]pyridine 15. (45%),
mp 64–65 ◦C (light petroleum); dH 2.15 (2H, qn, J 7.4,
CH2CH2CH2), 2.97 (2H, t, J 7.4, CH2Ar), 3.02 (2H, t, J 7.4,
CH2Ar), 6.84 (1H, d J 2.5, furoH-3), 7.51 (1H, s, pyridylH-8)
and 7.70 (1H, d, J 2.5, furoH-2); dC 24.14, 30.70, 33.65 (3 ×
CH2), 107.68, 114.64, 133.36, 145.67, 147.31, 147.74 and 162.15
(furopyridine).
6,7-Dimethoxy-2,3-dihydro-1H-cyclo◦penta[b]quinoline
27g.
(21%), mp 99–100 C (lit.,45 112–113 C; lit.,46 120–121 ◦C); dH
2.12 (2H, qn, J 7.6, CH2CH2CH2), 2.98 (2H, t, J 7.6, CH2), 3.04
(2H, t, J 7.6, CH2), 3.92 (3H, s, OMe), 3.94 (3H, s, OMe), 6.92
(1H, s, arH-8), 7.31 (1H, s, arH-5) and 7.68 (1H, s, arH-9); dC
23.59, 30.46, 34.34 (3 × CH2), 55.90, 55.94 (both OMe), 105.21,
107.53, 122.44, 129.10, 133.69, 143.99, 148.82, 151.34 and 165.24
(9 × arC).
◦
6,7-Dihydro-5H-cyclopenta[b]thieno[2,3-e]pyridine 16. (51%),
mp 84–85 ◦C; dH 2.21 (2H, qn, J 7.4, CH2CH2CH2), 3.03 (2H,
t, J 7.4, CH2Ar), 3.11 (2H, t, J 7.4, CH2Ar), 7.47 (1H, d, J 5.9)
and 7.52 (1H, d, J 5.9) (thienoH-2/3), 7.95 (1H, s, pyridylH-8);
6-Methyl-7-methoxy-2,3-dihydro-1H-cyclopenta[b]quinoline 27h.
(57%), mp 129–130 ◦C; dH 2.10 (2H, qn, J 7.6, CH2CH2CH2), 2.31
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(3H, s, Me), 2.96 (2H, t, J 7.4, CH2), 3.03 (2H, t, J 7.6, CH2), 3.84
(3H, s, Me), 6.85 (1H, s, arH-8) and 7.68 (2H, coincident singlets,
arH-5/9); dH (CD3)2SO 2.01 (2H, qn, J 7.6, CH2CH2CH2), 2.21
5,8-Dimethoxy-2,3-dihydro-1H-cyc◦lopenta[b]quinoline
29.
◦
(8%), mp 104–105 C (lit.,47 98–100 C); dH 2.11 (2H, qn, J 7.5,
CH2CH2CH2), 3.00 (2H, td, Jt 7.5, Jd 1.0, CH2Ar), 3.13 (2H, t,
J 7.5, CH2Ar), 3.86 (3H, s, OMe), 3.94 (3H, s, OMe), 6.61 (1H,
d, J 8.8) and 6.77 (1H, d, J 8.8) (arH-6/7), 8.22 (1H, s, arH-9);
dC 22.62, 29.64, 33.86 (3 × CH2), 54.76, 54.89 (OMe), 101.89,
104.76, 119.58, 124.20, 134.44, 138.64, 147.73, 148.24 and 166.25
(9 × arC).
=
=
(3H, s, Me), 2.88 (4H, m, CH2C C and CH2C N), 3.80 (3H, s,
OMe), 7.03 (1H, s, arH-8), 7.55 (1H, s) and 7.74 (1H, s) (arH-5/9);
dC 17.01 (Me), 23.62, 29.49, 34.24 (3 × CH2), 55.34 (OMe), 103.72,
126.75, 129.05, 129.20, 130.93, 134.54, 143.07, 156.21 and 164.83
(9 × arC).
9,10-Dihydro-8H-benzo[h]cyclopenta[b]quinoline
31. (74%
7-Hydroxy-2,3-dihydro-1H-cyclopenta[b]quinoline 27i. (30%),
mp 142–143 ◦C; dH (CD3)2SO 2.08 (2H, qn, J 7.6 CH2CH2CH2),
2.96 (4H, m, ArCH2 and ArꢁCH2), 6.96 (1H, d, J 2.4, arH-8), 7.13
(1H, dd, J 8.9, 2.4, arH-6), 7.63 (1H, s, arH-9), 7.70 (1H, d, J
8.9, arH-5) and 9.35 (1H, s, OH); dC (CD3)2SO 23.19, 30.00, 33.68
(3 × CH2), 108.45, 120.09, 128.14, 128.48, 128.91, 135.22, 141.99,
154.44 and 164.02 (9 × arC).
from 30a; 72% from 30b), mp 115–116 ◦C; dH 2.23 (2H, qn, J
7.9, CH2CH2CH2), 3.07 (2H, t, J 7.9, ArCH2), 3.26 (2H, t, J 7.9,
ArCH2), 7.59 (1H, d, J 8.5), 7.70 (3H, m), 7.84 (1H, s, arH-7),
7.89 (1H, dd, J 7.9, 0.9 Hz) and 9.35 (1H, d, J 8.5); dC 23.57,
30.49, 34.70 (3 × CH2), 124.12, 124.90, 125.52, 126.30, 126.48,
127.34, 127.55, 130.60, 131.42, 133.20, 135.85, 145.32 and 166.14
(13 × arC).
7-N,N-Dimethylamino-2,3-dihydro-1H-cyclopenta[b]quinoline
27j. (6%), mp 122–123 ◦C; dH 2.10 (2H, qn, J 7.5, CH2CH2CH2),
2.96 (2H, t, J 7.5, ArCH2), 2.98 (6H, s, NMe2), 3.03 (2H, t, J 7.5,
ArCH2), 6.71 (1H, d, J 2.6, arH-8), 7.21 (1H, dd, J 9.2, 2.6, arH-6),
7.65 (1H, s, arH-9) and 7.80 (1H, d, J 9.2, arH-5); dC 23.48, 30.57,
34.14 (3 × CH2), 40.88 (NMe2), 105.75, 118.27, 128.70, 128.83,
128.87, 135.75, 141.29, 148.18 and 163.56 (9 × arC).
Acknowledgements
Enterprise Ireland, Forbairt, the Irish American Partnership
and Dublin City University are gratefully acknowledged for
supporting this work.
A higher yield (35%) of 7-N,N-dimethylamino-2,3-dihydro-
1H-cyclopenta[b]quinoline 27j was obtained following similar
irradiation in the presence of added trifluoroacetic acid (1 equiv.,
2.4 mM). Isolation, by diethyl ether extraction and chromatogra-
phy, followed initial adjustment of the irradiated solution to pH
∼8 by addition of 10% aq. sodium carbonate solution.
Notes and references
1 M. Balasubramanian and J. G. Keay, in Comprehensive Heterocyclic
Chemistry II, ed. A. R. Katritzky, C. W. Rees and E. F. V. Scriven,
Pergamon Press, Oxford, 1996, vol. 5, p. 245.
2 G. Jones, in Comprehensive Heterocyclic Chemistry II, ed. A. R. Ka-
tritzky, C. W. Rees and E. F. V. Scriven, Pergamon Press, Oxford, 1996,
vol. 5, p. 167.
7-Amino-2,3-dihydro-1H-cyclopenta[b]quinoline 27k. (26%),
mp 121–122 ◦C; dH 2.00 (2H, qn, J 7.6, CH2CH2CH2), 2.85 (2H,
t, J 7.6, ArCH2), 2.94 (2H, t, J 7.6, ArCH2), 3.80 (2H, s, NH2),
6.67 (1H, d, J 2.4, arH-8), 6.89 (1H, dd, J 8.8, 2.4, arH-6), 7.47
(1H, s, arH-9) and 7.68 (1H, d, J 8.8, arH-5); dC 23.51, 30.37, 33.93
(3 × CH2), 107.91, 120.13, 128.39, 128.46, 128.59, 135.75, 142.14,
143.81 and 163.90 (9 × arC).
7-Acetoxy-2,3-dihydro-1H-cyclopenta[b]quinoline 27l and 5-
hydroxy-2,3-dihydro-1H-cyclopenta[b]quinoline 26lꢀ. The two
products that remained following irradiation of 2-(3-acetoxy-
benzylidene)cyclopentanone O-acetyloxime were separated on a
silica column with mobile phase 10 : 90 light petroleum–ethyl
acetate to give:
3 For reviews of carbon–nitrogen double bond photochemistry see: (a) A.
Padwa, Chem. Rev., 1977, 77, 37–68; (b) A. C. Pratt, Chem. Soc.
Rev., 1977, 6, 63–81; (c) H. Suginome, in CRC Handbook of Organic
Photochemistry and Photobiology, ed. W. M. Horspool and F. Lenci,
CRC Press, Boca Raton, FL, 2nd edn, 2004, 94/1-94/55.
4 J. Glinka, Pol. J. Chem., 1979, 53, 2143–2148.
5 D. Armesto, M. G. Gallego and W. M. Horspool, J. Chem. Soc., Perkin
Trans. 1, 1989, 1623–1626.
6 W. Verboom, P. J. S. S. Van Eijk, P. G. M. Conti and D. N. Reinhoudt,
Tetrahedron, 1989, 45, 3131–3138.
7 A. Okami, T. Arai, H. Sakuragi and K. Tokumaru, Chem. Lett., 1984,
289–292; K. Ikoma, A. Okami, T. Arai, H. Sakuragi and K. Tokumaru,
Tetrahedron Lett., 1984, 25, 5161–5164.
8 A. C. Pratt and Q. Abdul-Majid, J. Chem. Soc., Perkin Trans. 1, 1986,
1691–1693.
9 V. H. M. Elferink and H. J. T. Bos, J. Chem. Soc., Chem. Commun.,
1985, 882–883.
10 R. J. Olsen, Tetrahedron Lett., 1991, 32, 5235–5238; R. J. Olsen,
(i)
7-Acetoxy-2,3-dihydro-1H-cyclopenta[b]quinoline
27l.
J. Photochem. Photobiol., A, 1997, 103, 91–94.
(20%), mp 118–119 ◦C; dH 2.13 (2H, qn, J 7.5, CH2CH2CH2),
2.27 (3H, s, MeCO), 2.99 (2H, td, Jt 7.5, Jd 1.2, ArCH2), 3.07 (2H,
t, J 7.5, ArꢁCH2), 7.27 (1H, dd, J 8.9, 2.5, arH-6), 7.39 (1H, d, J
2.5, arH-8), 7.76 (1H, s, arH-9) and 7.95 (1H, d, J 8.9, arH-5);
dC 20.17 (Me), 22.59, 29.49, 33.45 (3 × CH2), 117.21, 122.27,
126.62, 128.84, 129.05, 135.35, 144.38, 146.81, 166.94 (9 × arC)
11 J. Suwin´ski and M. A. A. Mohamed, Pol. J. Chem., 2001, 75, 965–974;
M. A. A. Mohamed, U. Siedlecka and J. Suwin´ski, Pol. J. Chem., 2003,
77, 577–590.
12 See, for example: (a) M. P. Cava, P. Stern and K. Wakisaka, Tetrahedron,
1973, 29, 2245–2249; (b) R. G. F. Giles and M. V. Sargent, J. Chem.
Soc., Perkin Trans. 1, 1974, 2447–2450.
13 Closure at the naphthyl 3-position would have yielded the known
2,3-dihydro-1H-4-aza-cyclopenta[b]anthracene, mp 181–184 ◦C E.
Taffarel, S. Chirayil, R. Thummel and P. Randolph, J. Org. Chem.,
1994, 59, 823–828.
14 For reviews see: (a) E. V. Blackburn and C. J. Timmons, Q. Rev. Chem.
Soc., 1969, 23, 482–503; (b) W. H. Laarhoven, Recl. Trav. Chim. Pays-
Bas, 1983, 102, 185–204; (c) F. B. Mallory and C. W. Mallory, Org.
React. (N. Y.), 1984, 30, 1–456; (d) L. Hazai and G. Hornya´k, ACH
Models Chem., 1998, 135, 493–514; (e) A. Gilbert, in CRC Handbook
of Organic Photochemistry and Photobiology, ed. W. Horspool and P.-
S. Song, CRC Press LLC, Boca Raton, Florida, 1st edn, 1995, pp. 291–
300; (f) A. Gilbert, in CRC Handbook of Organic Photochemistry and
=
and 168.53 (C O).
(ii) 5-Hydroxy-2,3-dihydro-1H-cyclopenta[b]quinoline 26lꢀ.
(17%), mp 74–75 ◦C; dH (CD3)2SO 2.14 (2H, qn, J 7.5,
CH2CH2CH2), 3.05 (4H, m, 2 × ArCH2), 6.98 (1H, dd, J 8.0, 1.6,
arH-6) and 7.28 (1H, dd, J 8.0, 1.6, arH-8), 7.32 (1H, t, J 8.0,
arH-7), 8.03 (1H, s, arH-9) and 8.29 (1H, s, OH); dC 23.65, 30.47,
34.11 (3 × CH2), 109.15, 117.65, 126.39, 127.53, 130.35, 136.60,
137.35, 151.49 and 165.70 (9 × arC).
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View Article Online
Photobiology, ed. W. Horspool and F. Lenci, CRC Press LLC, Boca
Raton, Florida, 2nd edn, 2004, 33/1-33/11.
15 J. B. M. Somers and W. H. Laarhoven, J. Photochem. Photobiol., A,
1987, 40, 125–143; J. B. M. Somers and W. H. Laarhoven, J. Photochem.
Photobiol., A, 1989, 48, 353–374.
16 F. D. Lewis and R. S. Kalgutkar, J. Phys. Chem. A, 2001, 105, 285–291;
F. D. Lewis, T. L. Kurth and R. S. Kalgutkar, Chem. Commun., 2001,
1372–1373.
Guindon, B. Gue´rin and S. R. Landry, Org. Lett., 2001, 3, 2293–2296;
K. Narasaka and M. Kitamura, Eur. J. Org. Chem., 2005, 4505–4519.
30 A. R. Forrester, M. Gill, J. S. Sadd and R. H. Thomson, J. Chem. Soc.,
Perkin Trans. 1, 1979, 612–615.
31 S. Atmaram, A. R. Forrester, M. Gill and R. H. Thomson, J. Chem.
Soc., Perkin Trans. 1, 1981, 1721–1724.
32 A. J. McCarroll and J. C. Walton, J. Chem. Soc., Perkin Trans. 2, 2000,
1868–1875.
17 C. S. Mallory and F. B. Mallory, J. Org. Chem., 1964, 29, 3373–3377;
H. Jungmann, H. Gusten and D. Schulte-Frohlinde, Chem. Ber., 1968,
101, 2690–2696.
18 For reviews of the NEER principle see: (a) H. J. Jacobs and E.
Havinga, Adv. Photochem., 1979, 11, 305–373; (b) U. Mazzucato and
F. Momichioli, Chem. Rev., 1991, 91, 1679–1719.
19 T. Wismonski-Knittel, G. Fischer and E. Fischer, J. Chem. Soc., Perkin
Trans. 2, 1974, 1930–1940.
20 Y. Ittah, A. Jakob, K. A. Muszkat, N. Castel and E. Fischer,
J. Photochem. Photobiol., A, 1991, 56, 239–247.
21 V. F. Razumov, S. P. Kazakov and T. S. Zyubina, High Energy Chem.,
1996, 30, 257–260.
22 (a) W. H. Laarhoven, T. J. H. M. Cuppen and R. J. F. Nivard,
Tetrahedron, 1970, 26, 4865–4881; (b) K. A. Muszkat, G. Seger and
S. Sharafi-Ozeri, J. Chem. Soc., Faraday Trans. 2, 1975, 71, 1529–1544.
23 F. B. Mallory and C. W. Mallory, J. Am. Chem. Soc., 1972, 94, 6041–
6048.
33 A. J. McCarroll and J. C. Walton, Chem. Commun., 2000, 351–352.
34 M. Kitamura, Y. Mori and K. Narasaka, Tetrahedron Lett., 2005, 46,
1083–1086.
35 A. Padwa and F. Albrecht, J. Am. Chem. Soc., 1972, 94, 1000–1002; A.
Padwa and F. Albrecht, J. Am. Chem. Soc., 1974, 96, 4849–4857; A.
Padwa and F. Albrecht, J. Org. Chem., 1974, 39, 2361–2366.
36 A. Padwa and F. Albrecht, Tetrahedron Lett., 1974, 1083–1086.
37 P. Baas, H. Cerfontain and P. C. M. Van Noort, Tetrahedron, 1981, 37,
1583–1588.
38 D. Armesto, W. M. Horspool and F. Langa, J. Chem. Soc., Chem.
Commun., 1987, 1874–1875; D. Armesto, M. G. Gallego and W. M.
Horspool, Tetrahedron Lett., 1990, 31, 2475–2478; D. Armesto, A. R.
Agarrabeitia, W. M. Horspool and M. G. Gallego, J. Chem. Soc.,
Chem. Commun., 1990, 934–936; D. Armesto, M. G. Gallego and
W. M. Horspool, Tetrahedron, 1990, 46, 6185–6192; D. Armesto, W. M.
Horspool, F. Langa and A. Ramos, J. Chem. Soc., Perkin Trans. 1,
1991, 223–228; D. Armesto, W. M. Horspool, M. G. Gallego and
A. R. Agarrabeitiae, J. Chem. Soc., Perkin Trans. 1, 1992, 163–169; D.
Armesto, W. M. Horspool, M. J. Manchen˜o and M. J. Ortiz, J. Chem.
Soc., Perkin Trans. 1, 1992, 2325–2329; D. Armesto and A. Ramos,
Tetrahedron, 1993, 49, 7159–7168; D. Armesto, M. J. Ortiz, A. Ramos,
W. M. Horspool and E. P. Mayoral, J. Org. Chem., 1994, 59, 8115–
8124; D. Armesto, A. Ramos and E. P. Mayoral, Tetrahedron Lett.,
1994, 35, 3785–3788; D. Armesto, M. G. Gallego, W. M. Horspool and
A. R. Agarrabeitia, Tetrahedron, 1995, 51, 9223–9240; D. Armesto, A.
Ramos, E. P. Mayoral, M. J. Ortiz and A. R. Agarrabeitia, Org. Lett.,
2000, 2, 183–186.
24 F. D. Lewis, R. S. Kalgutkar and J.-S. Yang, J. Am. Chem. Soc., 2001,
123, 3878–3884.
25 R. Alonso, P. J. Campos, B. Garcia and M. A. Rodriguez, Org. Lett.,
2006, 8, 3521–3523.
26 M. Hasebe, K. Kogawa and T. Tsuchiya, Tetrahedron Lett., 1984, 25,
3887–3890; M. Hasebe and T. Tsuchiya, Tetrahedron Lett., 1986, 27,
3239–3242; M. Hasebe and T. Tsuchiya, Tetrahedron Lett., 1987, 28,
6207–6210; M. Hasebe and T. Tsuchiya, Tetrahedron Lett., 1988, 29,
6287–6290.
27 A. J. McCarroll and J. C. Walton, J. Chem. Soc., Perkin Trans. 2, 2000,
2399–2409; E. M. Scanlan, A. M. Z. Slawin and J. C. Walton, Org.
Biomol. Chem., 2004, 716–724; G. A. DiLabio, E. M. Scanlan and J. C.
Walton, Org. Lett., 2005, 7, 155–158; E. M. Scanlan and J. C. Walton,
Helv. Chim. Acta, 2006, 89, 2133–2143.
39 M. Onda and K. Takeuchi, Chem. Pharm. Bull., 1975, 23, 677–680.
40 L. Birkofer, S. M. Kim and H. D. Engels, Chem. Ber., 1962, 95, 1495–
1504.
41 W. H. Perkin and S. G. P. Plant, J. Chem. Soc., 1928, 639–646.
42 E. A. Fehnel, J. Org. Chem., 1966, 31, 2899–2902.
43 E. C. Taylor, J. E. Macor and L. G. French, J. Org. Chem., 1991, 56,
1807–1812.
28 J. Laleve´e, X. Allonas, J. P. Fouassier, H. Tachi, A. Izumitani, M. Shirai
and M. Tsunooka, J. Photochem. Photobiol., A, 2002, 151, 27–37 and
references therein.
29 J. Boivin, A.-M. Schiano and S. Z. Zard, Tetrahedron Lett., 1994, 35,
249–252; J. Boivin, E. Fouquet and S. Z. Zard, Tetrahedron, 1994, 50,
1745–1756; J. Boivin, E. Fouquet and S. Z. Zard, Tetrahedron, 1994,
50, 1757–1768; J. Boivin, E. Fouquet, A.-M. Schiano and S. Z. Zard,
Tetrahedron, 1994, 50, 1769–1776; S. Z. Zard, Synlett, 1996, 1148–1154;
A. G. Fallis and I. M. Brinza, Tetrahedron, 1997, 53, 17543–17594; X.
Lin, D. Stien and S. M. Weinreb, Org. Lett., 1999, 1, 637–639; Y.
44 H. Miyashita, Yakugaku Zasshi, 1976, 96, 968–983, (Chem. Abstr.,
1977, 86, 89564h).
45 W. Borsche and J. Barthenheier, Justus Liebigs Ann. Chem., 1941, 548,
50–63.
46 Y. Arata and S. Sugasawa, Chem. Pharm. Bull., 1961, 9, 104.
47 J. L. Lim, S. Chirayil and R. P. Thummel, J. Org. Chem., 1991, 56,
1492–1500.
3786 | Org. Biomol. Chem., 2007, 5, 3778–3786
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